The Pediatric Oncology Group (POG) is a multi-institutional, multidisciplinary cooperative Group whose goal is to control cancer among children and adolescents by therapeutic research aimed at improving the survival and quality of life. The 101 institutions and 1,906 individual members of POG pool their knowledge and resources to jointly develop and conduct a wide variety of large-scale clinical and laboratory studies. Member investigators include pediatric oncologists, pathologists, surgeons, radiation therapists, diagnostic radiologists, statisticians, clinical research assistants, oncology nurse specialists, and others who cooperate to improve the outcomes of treatment and better understand the biology of childhood cancer. Reference laboratories conduct an array of adjunct studies of biologic samples for genetic, molecular, and cellular characteristics with subsequent correlation of biologic features with patient characteristics and outcome, providing unique opportunities to address scientific questions relating to risk assessment, epidemiology, pathobiology and other cancer-related topics. The overall aims of this five-year renewal application are to increase cure rates of all forms of childhood cancer while simultaneously reducing the acute and late consequences of treatment by design of risk-based therapies. We also aim to increase accruals, reduce barriers to enrollment, improve long-term follow-up, and extend the benefits of clinical trials participation. Traditional outcome analyses and translational research will be supplemented by innovative studies of alternative endpoints, including costs and quality of life. The Operations Office is the central Group headquarters and provides the staff and support for the overall scientific, administrative, and fiscal management of the Group. The Operations Office functions include responsibilities for all interactions with NCI, review of individual and institutional membership status and performance, maintenance of the Group bibliography, responsibility for convening and conducting semiannual meetings, distribution of monthly mailings and minutes, oversight of quality control and institutional audits, responsibility for preparation and coordination of all protocols from concept/LOI through activation and revisions and amendments as necessary, and provision of logistical and financial support to scientific committees, and disbursement of third party payments where relevant for participants without cooperative agreements from NCI. In all aspects of general scientific oversight and development of research plans and analyses for each disease studied, the Operations Office works closely with the Statistical Office in a seamless coordination of effort. This application requests renewed and continued ending for the Operations Office and for the scientific committees, reference laboratories and key personnel of the Group.